The cysteinyl (Cys) leukotrienes (LT) C 4, LTD 4, and LTE 4, are lipid mediators that have been implicated in the pathogenesis of asthma. The human LTD 4 receptor (CysLT 1 R) was recently cloned and characterized. The present work was undertaken to study the potential modulation of CysLT 1 R expression by the Th2 cytokines IL-13 and IL-4. In this study, we report that IL-13 up-regulates CysLT 1 R mRNA levels, with consequently enhanced CysLT 1 R protein expression and function in human monocytes and monocyte-derived macrophages. CysLT 1 R mRNA expression was augmented 2-to 5-fold following treatment with IL-13 and was due to enhanced transcriptional activity. The effect was observed after 4 h, was maximal by 8 h, and maintained at 24 h. IL-4, but not IFN-γ, induced a similar pattern of CysLT 1 R up-regulation. Monocytes pretreated with IL-13 or IL-4 for 24 h showed enhanced CysLT 1 R protein expression, as assessed by flow cytometry using a polyclonal anti-CysLT 1 R Ab. They also showed enhanced responsiveness to LTD 4, but not to LTB 4, in terms of Ca 2+ mobilization, as well as augmented chemotactic activity. Our findings suggest a possible mechanism by which IL-13 and IL-4 can modulate CysLT 1 R expression on monocytes and macrophages, and consequently their responsiveness to LTD 4, and thus contribute to the pathogenesis of asthma and allergic diseases.